Nutrition is perhaps the single most important factor influencing growth. The specific mechanisms as to the etiology of the growth retardation in the different nutritional deficiency diseases have not been delineated. Somatomedin, the growth hormone dependent factor in serum which mediates the action of growth hormone on the cartilage cell, is depressed after prolonged fasting or in severe malnutrition with elevated growth hormone levels. The effect of other nutritional deficiencies on growth hormone levels, somatomedin activity, or on cartilage glycosaminoglycan metabolism is not presently known. The overall objective of this research is to delineate the mechanism for severe growth retardation in specific nutritional deficiency diseases and to relate these factors to the control of normal growth and development. We will study the effects of variable amounts of dietary carbohydrate, protein and fat on body growth, plasma growth hormone concentration, somatomedin activity and cartilage GAGS metabolism in rats. In addition, selected specific amino acid, trace metal and vitamin deficiencies will be studied in a similar manner. Trace metal and vitamin deficiency studies will be done in chicks. Somatomedin will be assayed using both a bioassay and a radioreceptor assay to detect both biological activity and plasma concentration. The correlation of somatomedin activity and concentration, growth hormone concentration, cartilage GAGS metabolism, and microscopic bone changes will allow possible delineation of specific control mechanisms and may further advance our understanding of the role of nutrition in the modulation of somatomedin and body growth under physiologic conditions. Attempts will be made to define the length of time necessary to produce the specific hormonal and metabolic abnormalities and the length of time required for reversal of these effects.